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Late Sodium Current Blockade in High-Risk ICD Patients - CCC - Lead Application

高危 ICD 患者的晚期钠电流阻断 - CCC - 先导应用

基本信息

批准号：
8392240
负责人：
Wojciech Zareba
金额：
$ 40.71万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-25 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8392240
关键词：
Action Potentials Address Adrenergic beta-Antagonists Adverse effects Amiodarone Anti-Arrhythmia Agents Arrhythmia Atrial Fibrillation Calcium Cardiac Cardiomyopathies Cells Cessation of life Clinical Clinical Trials Controlled Clinical Trials Data Data Coordinating Center Development Double-Blind Method Effectiveness Enrollment Event Exercise Heart failure Hospitalization Impairment Implantable Defibrillators Ischemia Lead Left Lidocaine Measures Medical Minnesota Minor Molecular Structure Myocardial Myocardial Infarction Myocardial Ischemia Myocardium National Heart, Lung, and Blood Institute Patients Pharmaceutical Preparations Piperazines Placebo Control Placebos Play Process Property Quality of life Questionnaires Randomized Records Recurrence Relaxation Risk Role Safety Shock Sodium Sodium Channel Sotalol Stress Tachyarrhythmias Testing Torsades de Pointes Ventricular Ventricular Arrhythmia Ventricular Fibrillation Ventricular Tachycardia Walking abstracting diabetic patient effective therapy follow-up glycemic control high risk implantable device improved interest mortality novel pre-clinical public health relevance ranolazine

项目摘要

DESCRIPTION (provided by applicant): There are limited treatment options for patients at high risk of ventricular arrhythmic events. Beta- blockers alone do not provide enough protection, sotalol has limited effectiveness, and amiodarone although effective in some groups of patients is used infrequently due to its side effects and limitations of a long-term use. Ischemia and cardiomyopathies are associated with a sodium overload of myocardial cells. Late sodium current plays a pivotal role in this process. Sodium overload leads to calcium overload of myocardial cells with consequent increased vulnerability of myocardium to ventricular tachyarrhythmias as well as increased impairment of diastolic relaxation of myocardium thereby augmenting the risk of ischemia and myocardial damage. Ranolazine is a novel drug with anti-ischemic and anti-arrhythmic properties that uniquely blocks late sodium current, decreases intracellular calcium overload, and improves diastolic relaxation of the ventricles. The anti-ischemic and anti-arrhythmic properties of ranolazine might decrease the likelihood of arrhythmic events and improve the clinical course of patients at the risk for ventricular arrhythmias. We propose a randomized double-blind placebo-controlled clinical trial enrolling 1,200 high-risk ICD patients who will be treated with ranolazine or placebo in addition to optimal medical therapy. Primary aim of the study is to determine whether ranolazine administration in high-risk patients with ICDs contributes to a decrease in the number of patients reaching a composite arrhythmia endpoint consisting of ventricular tachycardia or fibrillation requiring appropriate ICD shocks, or death (whichever occurs first). Secondary aims of the study are: 1) to determine whether ranolazine administration will decrease the likelihood of composite primary endpoints consisting of hospitalization for cardiac causes or death, 2) to determine whether ranolazine administration will decrease the likelihood of a composite secondary endpoint consisting of CHF hospitalization or death, 3) to determine whether ranolazine therapy will decrease the number of repeated hospitalizations for cardiac causes, 4) to assess whether ranolazine administration will decrease the likelihood of repeated ICD therapies, 5) to evaluate whether ranolazine administration will decrease the likelihood of appropriate ICD shocks, 6) to determine whether ranolazine therapy will be associated with improvement in exercise capacity measured by the 6-minute walk test (6MWT) and in the quality of life measured by the Minnesota Leaving with Heart Failure Questionnaire (MLHFQ), and 7) to evaluate the safety of ranolazine therapy utilizing ICD interrogation data documenting all types of ventricular tachyarrhythmias (including torsade de pointes). This proposal consists of two clustered applications covering respective components of the trial: Clinical Core - Leading Application, and Data Coordination Center. (End of Abstract)

描述（由申请人提供）：